Acquired resistance to innate immune clearance promotes Klebsiella pneumoniae ST258 pulmonary infection
Danielle Ahn, Hernán Peñaloza, Zheng Wang, Matthew Wickersham, Dane Parker, Purvi Patel, Antonius Koller, Emily I. Chen, Susan M. Bueno, Anne-Catrin Uhlemann, Alice Prince
Danielle Ahn, Hernán Peñaloza, Zheng Wang, Matthew Wickersham, Dane Parker, Purvi Patel, Antonius Koller, Emily I. Chen, Susan M. Bueno, Anne-Catrin Uhlemann, Alice Prince
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Research Article Infectious disease Pulmonology

Acquired resistance to innate immune clearance promotes Klebsiella pneumoniae ST258 pulmonary infection

Abstract

Adaptive changes in the genome of a locally predominant clinical isolate of the multidrug-resistant Klebsiella pneumoniae ST258 (KP35) were identified and help to explain the selection of this strain as a successful pulmonary pathogen. The acquisition of 4 new ortholog groups, including an arginine transporter, enabled KP35 to outcompete related ST258 strains lacking these genes. KP35 infection elicited a monocytic response, dominated by Ly6Chi monocytic myeloid-derived suppressor cells that lacked phagocytic capabilities, expressed IL-10, arginase, and antiinflammatory surface markers. In comparison with other K. pneumoniae strains, KP35 induced global changes in the phagocytic response identified with proteomics, including evasion of Ca2+ and calpain activation necessary for phagocytic killing, confirmed in functional studies with neutrophils. This comprehensive analysis of an ST258 K. pneumoniae isolate reveals ongoing genetic adaptation to host microenvironments and innate immune clearance mechanisms that complements its repertoire of antimicrobial resistance genes and facilitates persistence in the lung.

Authors

Danielle Ahn, Hernán Peñaloza, Zheng Wang, Matthew Wickersham, Dane Parker, Purvi Patel, Antonius Koller, Emily I. Chen, Susan M. Bueno, Anne-Catrin Uhlemann, Alice Prince

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Figure 6

Comparative genomics of KP35, NR1155, published ST258 strains, and the KPPR1 reference strain.

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Comparative genomics of KP35, NR1155, published ST258 strains, and the K...
(A) Whole-genome alignment of the 4 K. pneumoniae genomes. The de novo–assembled KP35 draft genome and 2 other ST258 reference genomes (NJST258-1 and NJST258-2), aligned to the published ATCC-43816-KPPR1 genome. From the inner to the outer circles: scale bar, GC content, GC skew, KP35, NJST258-1, NJST258-2, ATCC-43816-KPPR1. The location of the KP35 special orthologous groups (OGs), in particular ArcD, were marked. (B) Venn diagram of the proteome OGs, KP35, ATCC-43816-KPPR1, and NJST258-1 showing the number of common and distinct OGs between KP35, ATCC-43816-KPPR1, and NJST258-1. (C) RaxML phylogenetic tree representing genetic origins of ATCC-43816-KPPR1, NR1155, KP35, and multiple clinical isolates of ST258. The tree was based on 79,458 concatenated core genome SNPs of the KP35 and 11 other published K. pneumoniae genomes. The multilocus sequence type of each isolate follows in parentheses. Bar represents ~2,000 SNPs.